A genome-wide association study in 10,000 individuals links plasma N-glycome to liver disease and anti-inflammatory proteins

Sodbo Sharapov, Anna Timoshchuk, Olga Zaytseva, Denis E. Maslov, Anna Soplenkova, Elizaveta E. Elgaeva, Evgeny S. Tiys, Massimo Mangino, Clemens Wittenbecher, Lennart Karssen, Maria Timofeeva, Arina Nostaeva, Frano Vuckovic, Irena Trbojević-Akmačić, Tamara Štambuk, Sofya Feoktistova, Nadezhda A. Potapova, Viktoria Voroshilova, Frances Williams, Dragan Primorac, Jan Zundert, Michel Georges, Karsten Suhre, Massimo Allegri, Nishi Chaturvedi, Malcolm Dunlop, Matthias B. Schulze, Tim Spector, Yakov A. Tsepilov, Gordan Lauc and Yurii S. Aulchenko ()
Additional contact information
Sodbo Sharapov: Lomonosov Moscow State University
Anna Timoshchuk: Lomonosov Moscow State University
Olga Zaytseva: Genos Glycoscience Research Laboratory
Denis E. Maslov: Lomonosov Moscow State University
Anna Soplenkova: Lomonosov Moscow State University
Elizaveta E. Elgaeva: Institute of Cytology and Genetics
Evgeny S. Tiys: Institute of Cytology and Genetics
Massimo Mangino: Lambeth Palace Road
Clemens Wittenbecher: German Institute of Human Nutrition Potsdam-Rehbruecke
Lennart Karssen: ’s-Hertogenbosch
Maria Timofeeva: The University of Edinburgh
Arina Nostaeva: Institute of Cytology and Genetics
Frano Vuckovic: Genos Glycoscience Research Laboratory
Irena Trbojević-Akmačić: Genos Glycoscience Research Laboratory
Tamara Štambuk: Genos Glycoscience Research Laboratory
Sofya Feoktistova: Institute of Cytology and Genetics
Nadezhda A. Potapova: Russian Academy of Sciences
Viktoria Voroshilova: Institute of Cytology and Genetics
Frances Williams: Lambeth Palace Road
Dragan Primorac: St. Catherine Specialty Hospital
Jan Zundert: ZOL
Michel Georges: University of Liège
Karsten Suhre: Education City
Massimo Allegri: Centre Lemanique d’antalgie et neuromodulation – EHC
Nishi Chaturvedi: MRC Unit for Lifelong Health & Ageing University College London
Malcolm Dunlop: The University of Edinburgh
Matthias B. Schulze: German Institute of Human Nutrition Potsdam- Rehbruecke
Tim Spector: Lambeth Palace Road
Yakov A. Tsepilov: Institute of Cytology and Genetics
Gordan Lauc: Genos Glycoscience Research Laboratory
Yurii S. Aulchenko: Lomonosov Moscow State University

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract More than a half of plasma proteins are N-glycosylated. Most of them are synthesized, glycosylated, and secreted to the bloodstream by liver and lymphoid tissues. While associations with N-glycosylation are implicated in the rising number of liver, cardiometabolic, and immune diseases, little is known about the genetic regulation of this process. Here, we performed the largest genome-wide association study of N-glycosylation of the blood plasma proteome in 10,000 individuals. We doubled the number of genetic loci known to be associated with blood N-glycosylation by identifying 16 novel loci and prioritizing 13 novel genes contributing to N-glycosylation. Among these were the GCKR, TRIB1, HP, SERPINA1 and CFH genes. These genes are predominantly expressed in the liver and show a previously unknown genetic link between plasma protein N-glycosylation, metabolic and liver diseases, and inflammatory response. By integrating glycomics, proteomics, transcriptomics, and genomics, we provide a resource that facilitates deeper exploration of disease pathogenesis and supports the discovery of glycan-based biomarkers.

Date: 2025
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DOI: 10.1038/s41467-025-60431-y

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